The goal of Project I is to define the dynamic properties of the olivo-cerebellar and neocortico-cerebellar circuits in the context of single cell physiological properties and neuronal connectivity. This project will address three interrelated specific aims. A: The role of different voltage and gated currents in Purkinje cell integration, from a molecular biological and biophysical perspective. This study will concern the (alpha1A channels and their regulation by PYK2 in native and heterologous expressed conditions, and in channelopathic systems. The results will be put into the context of two photon imaging and patch clamp electrophysiology. In addition, parallel/climbing fibers interaction on Purkinje cells concerning plasticity vs. dendritic cytotoxicity will be addressed. B: The role of electrotonic coupling and subthreshold oscillations in the organization of the olivocerebellar system will be studied as an example of a distributed parallel network. This effort will entail voltage-dependent dye imaging, intracellular recordings and mathematical modeling. C: Will attempt to determine the organization of inferior olivary dynamics and rhythmicity in relation to the control of movements by in vivo motor cortex stimulation in rodents.